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Pharmacology & Therapeutics Oct 2023In 2015, oncolytic virotherapy was approved for clinical use, and in 2017, recombinant adeno-associated virus (AAV) delivery was also approved. However, systemic... (Review)
Review
In 2015, oncolytic virotherapy was approved for clinical use, and in 2017, recombinant adeno-associated virus (AAV) delivery was also approved. However, systemic administration remains challenging due to the limited number of viruses that successfully reach the target site. Although the US Food and Drug Administration (FDA) permits the use of higher doses of AAV to achieve greater rates of transduction, most AAV still accumulates in the liver, potentially leading to toxicity there and elsewhere. Targeting the tumor microenvironment is a promising strategy for cancer treatment due to the critical role of the tumor microenvironment in controlling tumor progression and influencing the response to therapies. Newly discovered evidence indicates that administration routes focusing on the tumor microenvironment can promote delivery specificity and transduction efficacy within the tumor. Here, we review approaches that involve modifying viral surface features, modulating the immune system, and targeting the physicochemical characteristics in tumor microenvironment to regulate therapeutic delivery. Targeting tumor acidosis presents advantages that can be leveraged to enhance virotherapy outcomes and to develop new therapeutic approaches that can be integrated with standard treatments.
Topics: Humans; Tumor Microenvironment; Neoplasms; Oncolytic Virotherapy; Dependovirus
PubMed: 37657673
DOI: 10.1016/j.pharmthera.2023.108521 -
Molecular and Cellular Biochemistry Nov 2023Viral infection is a kind of cellular stress that leads to the changes in cellular metabolism. Many metabolic pathways in a host cell such as glycolysis, amino acid and... (Review)
Review
Viral infection is a kind of cellular stress that leads to the changes in cellular metabolism. Many metabolic pathways in a host cell such as glycolysis, amino acid and nucleotide synthesis are altered following virus infection. Both oncogenic and non-oncogenic viruses depend on host cell glycolysis for their survival and pathogenesis. Recent studies have shown that the rate of glycolysis plays an important role in oncolysis as well by oncolytic therapeutic viruses. During infection, viral proteins interact with various cellular glycolytic enzymes, and this interaction enhances the catalytic framework of the enzymes subsequently the glycolytic rate of the cell. Increased activity of glycolytic enzymes following their interaction with viral proteins is vital for replication and to counteract the inhibition of glycolysis caused by immune response. In this review, the importance of host cell glycolysis and the modulation of glycolysis by various viruses such as oncogenic, non-oncogenic and oncolytic viruses are presented.
PubMed: 36709223
DOI: 10.1007/s11010-023-04669-4 -
Chinese Medical Journal Jun 2024Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Its high recurrence rate and lack of effective control drugs result in a 5-year...
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Its high recurrence rate and lack of effective control drugs result in a 5-year survival rate of only about 10%. HCC is a tumor regulated by the immune system. Significant breakthroughs have occurred in treating solid tumors with immunotherapy in recent years. Various immunotherapies, such as immune checkpoint inhibitors (ICIs), including combination therapies, have demonstrated promising therapeutic effects in both clinical applications and research. Other immunotherapies, such as adoptive cell therapies and oncolytic viruses, are also emerging, offering hope for addressing long-term survival issues in HCC. This article reviews current commonly used immunotherapy strategies and the latest research findings for reference.
PubMed: 38855876
DOI: 10.1097/CM9.0000000000003060 -
Cancers Nov 2023Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving... (Review)
Review
Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that OVs can provide clinical benefits for patients with different types of tumors, at various stages, including metastatic and previously untreatable cases. When OVs are used in combination with chemotherapy, radiotherapy, immunotherapy, and other treatments, they can synergistically enhance the therapeutic effects. The concept of oncolytic virotherapy (OVT) was proposed in the early 20th century. With advancements in genetic engineering, genetically modified viruses can further enhance the efficacy of cancer immunotherapy. In recent years, global research on OV treatment of malignant tumors has increased dramatically. This article comprehensively reviews the findings from relevant research and clinical trials, providing an overview of the development of OVT and its application in the clinical treatment of head and neck cancer. The aim is to offer insights for future clinical and fundamental research on OVT.
PubMed: 37958464
DOI: 10.3390/cancers15215291 -
Life Sciences Mar 2024Tumor immunotherapy has become a new hotspot for cancer treatment. Various immunotherapies, such as immune checkpoint inhibitors, oncolytic viruses (OVs), cytokines, and... (Review)
Review
Tumor immunotherapy has become a new hotspot for cancer treatment. Various immunotherapies, such as immune checkpoint inhibitors, oncolytic viruses (OVs), cytokines, and cancer vaccines, have been used to treat tumors. They operate through different mechanisms, along with certain toxicities and side effects. Understanding the mechanisms by which immunotherapy modulates the immune system is essential for improving the efficacy and managing these adverse effects. This article discusses various currently approved cancer immunotherapy mechanisms and related agents approved by the Food and Drug Administration, the European Medicines Agency, and the Medicines and Medical Devices Agency. We also review the latest progress in immune drugs approved by the National Medical Products Administration, including monoclonal antibodies, cytokines, OVs, and chimeric antigen receptor-T cell therapy, to help understand the clinical application of tumor immunotherapy.
Topics: Humans; Pharmaceutical Preparations; Neoplasms; Immunotherapy; Antibodies, Monoclonal; Oncolytic Viruses; Cytokines
PubMed: 38242494
DOI: 10.1016/j.lfs.2024.122419 -
Signal Transduction and Targeted Therapy Sep 2023With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many...
With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Seroepidemiologic Studies; Lung Neoplasms; Apoptosis; Oncolytic Viruses; DNA
PubMed: 37743418
DOI: 10.1038/s41392-023-01603-4 -
Pathology, Research and Practice Aug 2023Neuroendocrine neoplasms (NENs) comprise malignancies involving neuroendocrine cells that often lead to fatal pathological conditions. Despite escalating global... (Review)
Review
Neuroendocrine neoplasms (NENs) comprise malignancies involving neuroendocrine cells that often lead to fatal pathological conditions. Despite escalating global incidences, NENs still have poor prognoses. Interestingly, research indicates an intricate association of tumor viruses with NENs. However, there is a dearth of comprehension of the complete scenario of NEN pathophysiology and its precise connections with the tumor viruses. Interestingly, several cutting-edge experiments became helpful for further screening of NET for the presence of polyomavirus, Human papillomavirus (HPV), Kaposi sarcoma-associated herpesvirus (KSHV), Epstein Barr virus (EBV), etc. Current research on the neuroendocrine tumor (NET) pathogenesis provides new information concerning their molecular mechanisms and therapeutic interventions. Of note, scientists observed that metastatic neuroendocrine tumors still have a poor prognosis with a palliative situation. Different oncolytic vector has already demonstrated excellent efficacies in clinical studies. Therefore, oncolytic virotherapy or virus-based immunotherapy could be an emerging and novel therapeutic intervention. In-depth understanding of all such various aspects will aid in managing, developing early detection assays, and establishing targeted therapeutic interventions for NENs concerning tumor viruses. Hence, this review takes a novel approach to discuss the dual role of tumor viruses in association with NENs' pathophysiology as well as its potential therapeutic interventions.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neuroendocrine Tumors; Herpesvirus 8, Human; Carcinoma, Neuroendocrine
PubMed: 37542862
DOI: 10.1016/j.prp.2023.154720 -
Immunotherapy Advances 2023Bispecific T-cell engagers (BiTEs) redirect endogenous T-cell populations to cells expressing tumour-associated antigens to induce tumour cell killing. This inherently... (Review)
Review
Bispecific T-cell engagers (BiTEs) redirect endogenous T-cell populations to cells expressing tumour-associated antigens to induce tumour cell killing. This inherently relies upon a cytotoxic T-cell population that is able to be recruited. In many cancers, immune checkpoints and other immunosuppressive factors in the tumour microenvironment lead to a population of anergic T-cells which cannot be redirected to tumour killing and thus impede the efficacy of BiTE therapy. Furthermore, there is evidence that BiTE therapy itself can increase immune checkpoint expression, and this is thought to be a major escape mechanism for the BiTE therapy blinatumomab. To overcome these inadequate T-cell responses, BiTEs may be combined with checkpoint inhibitors, chemotherapy, costimulatory molecules or oncolytic viruses. Study of these combinations is needed to expand the use of BiTEs in solid malignancies. This review covers the rationale, preclinical evidence and any clinical trials for these combination therapies and a few other less-studied combinations.
PubMed: 37599903
DOI: 10.1093/immadv/ltad013 -
Trends in Cancer Feb 2024Oncolytic viruses (OVs), viruses engineered to lyse tumor cells, work hand in hand with the immune response. While for decades the field isolated lytic capability and... (Review)
Review
Oncolytic viruses (OVs), viruses engineered to lyse tumor cells, work hand in hand with the immune response. While for decades the field isolated lytic capability and viral spread to increase response to virotherapy, there is now a wealth of research that demonstrates the importance of immunity in the OV mechanism of action. In this review, we will cover how OVs interact with the innate immune system to fully activate the adaptive immune system and yield exceptional tumor clearances as well as look forward at combination therapies which can improve clinical responses.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Adaptive Immunity; Neoplasms; Combined Modality Therapy
PubMed: 37880008
DOI: 10.1016/j.trecan.2023.09.012 -
Viruses Dec 2023Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple... (Review)
Review
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy by altering the wild-type virus and making it replication-defective; specific viral genes can be removed and replaced with a segment that holds a therapeutic gene, and this vector can be used as delivery vehicle for tissue specific gene delivery. Modified conditionally replicative-oncolytic adenoviruses target tumors exclusively and have been studied in clinical trials extensively. This comprehensive review seeks to offer a summary of adenovirus vectors, exploring their characteristics, genetic enhancements, and diverse applications in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing cancer therapy and the latest breakthroughs in vaccine clinical trials for various diseases. Additionally, we tackle current challenges and future avenues for optimizing adenovirus vectors, promising to open new frontiers in the fields of cell and gene therapies.
Topics: Humans; COVID-19 Vaccines; Virus Replication; Neoplasms; Genetic Vectors; Adenoviridae; Genetic Therapy; Vaccines
PubMed: 38140619
DOI: 10.3390/v15122378